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| | ==Crystal structure of the MRH domain of Glucosidase II beta bound to mannose== | | ==Crystal structure of the MRH domain of Glucosidase II beta bound to mannose== |
| - | <StructureSection load='4xqm' size='340' side='right' caption='[[4xqm]], [[Resolution|resolution]] 1.62Å' scene=''> | + | <StructureSection load='4xqm' size='340' side='right'caption='[[4xqm]], [[Resolution|resolution]] 1.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xqm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XQM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XQM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xqm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XQM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.625Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lvx|2lvx]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.84 3.2.1.84] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xqm OCA], [https://pdbe.org/4xqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xqm RCSB], [https://www.ebi.ac.uk/pdbsum/4xqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xqm ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xqm RCSB], [http://www.ebi.ac.uk/pdbsum/4xqm PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLU2B_SCHPO GLU2B_SCHPO]] Subunit of glucosidase 2, which cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins in the endoplasmic reticulum (ER). Specifically required for the cleavage of the final glucose. The subunit beta retains the catalytic subunit alpha in the ER.<ref>PMID:10464333</ref> <ref>PMID:19605557</ref> <ref>PMID:21471007</ref> | + | [https://www.uniprot.org/uniprot/GLU2B_SCHPO GLU2B_SCHPO] Subunit of glucosidase 2, which cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins in the endoplasmic reticulum (ER). Specifically required for the cleavage of the final glucose. The subunit beta retains the catalytic subunit alpha in the ER.<ref>PMID:10464333</ref> <ref>PMID:19605557</ref> <ref>PMID:21471007</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4xqm" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Alpha-glucosidase 3D structures|Alpha-glucosidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hydrolase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dahms, N M]] | + | [[Category: Schizosaccharomyces pombe 972h-]] |
| - | [[Category: Kim, J J.P]] | + | [[Category: Dahms NM]] |
| - | [[Category: Olson, L J]] | + | [[Category: Kim J-JP]] |
| - | [[Category: Sugar binding protein]] | + | [[Category: Olson LJ]] |
| Structural highlights
Function
GLU2B_SCHPO Subunit of glucosidase 2, which cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins in the endoplasmic reticulum (ER). Specifically required for the cleavage of the final glucose. The subunit beta retains the catalytic subunit alpha in the ER.[1] [2] [3]
Publication Abstract from PubMed
N-Glycans are modified as part of a quality control mechanism during glycoprotein folding in the endoplasmic reticulum (ER). Glucosidase II (GII) plays a critical role by generating monoglucosylated glycans that are recognized by lectin chaperones, calnexin and calreticulin. To understand how the hydrolytic activity of GIIalpha is enhanced by the mannose 6-phosphate receptor (MPR) homology domain (MRH domain) of its beta subunit, we now report a 1.6 A resolution crystal structure of the MRH domain of GIIbeta bound to mannose. A comparison of ligand-bound and unbound structures reveals no major difference in their overall fold, but rather a repositioning of side chains throughout the binding pocket, including Y372. Mutation of Y372 inhibits GII activity, demonstrating an important role for Y372 in regulating GII activity. Comparison of the MRH domains of GIIbeta, MPRs, and the ER lectin OS-9 identified conserved residues that are critical for the structural integrity and architecture of the carbohydrate binding pocket. As shown by nuclear magnetic resonance spectroscopy, mutations of the primary binding pocket residues and adjacent W409, all of which inhibit the activity of GII both in vitro and in vivo, do not cause a significant change in the overall fold of the GIIbeta MRH domain but impact locally the stability of the binding pocket. W409 does not directly contact mannose; rather, its indole ring is stabilized by binding into a hydrophobic pocket of an adjacent crystallographic neighbor. This suggests that W409 interacts with a hydrophobic region of the GIIbeta or GIIalpha subunit to modulate its effect on GII activity.
Crystal Structure and Functional Analyses of the Lectin Domain of Glucosidase II: Insights into Oligomannose Recognition.,Olson LJ, Orsi R, Peterson FC, Parodi AJ, Kim JJ, D'Alessio C, Dahms NM Biochemistry. 2015 Jul 7;54(26):4097-111. doi: 10.1021/acs.biochem.5b00256. Epub , 2015 Jun 24. PMID:26062005[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ D'Alessio C, Fernandez F, Trombetta ES, Parodi AJ. Genetic evidence for the heterodimeric structure of glucosidase II. The effect of disrupting the subunit-encoding genes on glycoprotein folding. J Biol Chem. 1999 Sep 3;274(36):25899-905. PMID:10464333
- ↑ Stigliano ID, Caramelo JJ, Labriola CA, Parodi AJ, D'Alessio C. Glucosidase II beta subunit modulates N-glycan trimming in fission yeasts and mammals. Mol Biol Cell. 2009 Sep;20(17):3974-84. Epub 2009 Jul 15. PMID:19605557 doi:E09-04-0316
- ↑ Stigliano ID, Alculumbre SG, Labriola CA, Parodi AJ, D'Alessio C. Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo. Mol Biol Cell. 2011 Jun 1;22(11):1810-23. doi: 10.1091/mbc.E11-01-0019. Epub 2011, Apr 6. PMID:21471007 doi:10.1091/mbc.E11-01-0019
- ↑ Olson LJ, Orsi R, Peterson FC, Parodi AJ, Kim JJ, D'Alessio C, Dahms NM. Crystal Structure and Functional Analyses of the Lectin Domain of Glucosidase II: Insights into Oligomannose Recognition. Biochemistry. 2015 Jul 7;54(26):4097-111. doi: 10.1021/acs.biochem.5b00256. Epub , 2015 Jun 24. PMID:26062005 doi:http://dx.doi.org/10.1021/acs.biochem.5b00256
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